Sinapic acid ameliorates paracetamol-induced acute liver injury through targeting oxidative stress and inflammation

Background Acetaminophen (paracetamol, APAP) overdose is the principal cause of acute liver injury (ALI) that leads to liver failure typified with oxidative stress, mitochondrial and lysosomal dysfunction and with few antidotes for this condition. Therefore, more effective therapeutics are urgently required. Sinapic acid is a phenolic phytochemical with significant antioxidant, anti-inflammatory and hepatoprotective potential. Rationale and purpose of the study This study was conducted to evaluate hepatoprotective effect of this phytochemical in acetaminophen-induced model of ALI. Methods and results Male C57BL/6 mice were treated p.o. with sinapic acid (10 or 50 mg/kg) 3 times at 72, 24, and 1 h before APAP (300 mg/kg; i.p.) challenge. Functional factors of liver dysfunction were determined along with hepatic assessment of oxidative stress and inflammatory indexes and histopathological analysis was also conducted. Sinapic acid (50 mg/kg) properly decreased serum levels of ALT, ALP, and AST besides reducing liver level of ROS, MDA, IL-6, TNF-alpha, NF-kB, and MPO and improved sirtuin 1, HO-1, Nrf2, SOD activity, and MMP with no significant effect on IL-1 beta and catalase activity in addition to decreasing activity of lysosomal enzymes including cathepsin B and beta-galactosidase. Also, sinapic acid at the higher dose ameliorated liver histopathological changes due to APAP and properly reversed NF-kB and Nrf2 immunoreactivity. Conclusions These findings show that sinapic acid pretreatment effectively protects liver against adverse and hepatotoxic effect of APAP through its antioxidant- and anti-inflammatory potential linked to NF-kB/Nrf2/HO-1 signaling and also via regulation of sirtuin 1, mitochondrial integrity, and lysosomal stabilization.